C-reactive protein (CRP) is the best-known acute phase protein. In humans, almost every type of inflammation is accompanied by an increase of CRP concentration. Until recently, the only known physiological function of CRP was the marking of cells to initiate their phagocytosis. This triggers the classical complement pathway up to C4, which helps to eliminate pathogens and dead cells. However, vital cells with reduced energy supply are also marked, which is useful in the case of a classical external wound because an important substrate for pathogens is disposed of, but is counterproductive at internal wounds (e.g., heart attack or stroke). This mechanism negatively affects clinical outcomes since it is established that CRP levels correlate with the prognosis of these indications. Here, we summarize what we can learn from a clinical study in which CRP was adsorbed from the bloodstream by CRP-apheresis. Recently, it was shown that CRP can have a direct effect on blood pressure in rabbits. This is interesting in regard to patients with high inflammation, as they often become tachycardic and need catecholamines. These two physiological effects of CRP apparently also occur in COVID-19. Parts of the lung become ischemic due to intra-alveolar edema and hemorrhage and in parallel CRP increases dramatically, hence it is assumed that CRP is also involved in this ischemic condition. It is meanwhile considered that most of the damage in COVID-19 is caused by the immune system. The high amounts of CRP could have an additional influence on blood pressure in severe COVID-19.
Patient: Male, 39-year-old Final Diagnosis: SARS-CoV-2 Symptoms: Fatigue • dyspnea • fever Medication: Dexamethasone • heparin Clinical Procedure: C-reactive protein apheresis Specialty: Immunology Objective: Unusual clinical course Background: High C-reactive protein (CRP) plasma levels in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are associated with poor prognosis. CRP, by activating the classical complement pathway and interacting with macrophages via Fc gamma receptors, can cause pulmonary inflammation with subsequent fibrosis. Recently, we have reported first-in-man CRP apheresis in a “high-risk” COVID-19 patient. Treatment was unfortunately clinically unsuccessful. Here, we report on successful CRP apheresis treatment in a “lower-risk” COVID-19 patient with respiratory failure. Case Report: A 39-year-old male patient suffering from fatigue, dyspnea, and fever for 4 days was referred to us. The patient had to be intubated. Polymerase chain reaction (PCR) analysis of a throat smear revealed SARS-CoV-2 infection. Mutation analysis revealed the VOC B . 1.1.7 variant. CRP levels were 79.2 mg/L and increased to 161.63 mg/L. Procalcitonin (PCT) levels were continuously normal (<0.5 ng/ml). Antibiotic therapy was started to avoid bacterial superinfection. CRP apheresis was performed once via central venous access. CRP levels declined from a maximum of 161.63 mg/L to 32.58 mg/L. No apheresis-associated adverse effects were observed. Subsequently, CRP plasma levels declined day by day and normalized on day 5. The patient was extubated on day 5 and discharged from the Intensive Care Unit (ICU) on day 6. A second low CRP peak (maximum 22.41 mg/L) on day 7 remained clinically inapparent. The patient was discharged in good clinical condition with a CRP level of 6.94 mg/L on day 8. Conclusions: SARS-CoV-2 infection can induce an uncontrolled CRP-mediated autoimmune response of ancient immunity. In this patient, the autoimmune response was potently and successfully suppressed by early selective CRP apheresis.
C-reactive protein (CRP), the prototype human acute phase protein, may be causally involved in various human diseases. As CRP has appeared much earlier in evolution than antibodies and nonetheless partly utilizes the same biological structures, it is likely that CRP has been the first antibody-like molecule in the evolution of the immune system. Like antibodies, CRP may cause autoimmune reactions in a variety of human pathologies. Consequently, therapeutic targeting of CRP may be of utmost interest in human medicine. Over the past two decades, however, pharmacological targeting of CRP has turned out to be extremely difficult. Currently, the easiest, most effective and clinically safest method to target CRP in humans may be the specific extracorporeal removal of CRP by selective apheresis. The latter has recently shown promising therapeutic effects, especially in acute myocardial infarction and COVID-19 pneumonia. This review summarizes the pros and cons of applying this novel technology to patients suffering from various diseases, with a focus on its use in cardiovascular medicine.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.